Page 256 - Haematologica March 2020

Y. Wang et al.
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Figure 3. Survival outcomes of the 24 Richter transformation (RT) patients who underwent stem cell transplantation (SCT). (A) Swimmers plot showing time from RT diagnosis to SCT (blue) and post-SCT survival (red; numbers indicate post-SCT survival in months). (B) Post-SCT survival for all patients who underwent SCT. CI: Confidence Interval.
DLBCL-type RT overall had a poor prognosis with a medi- an OS of only 12 months. Patients with RT who received no prior CLL treatment had a significantly better OS, with a median OS of approximately four years.
Our singular finding is that patients who received no prior CLL therapy had a favorable outcome. Further proof of this finding was provided in a prior phase II trial of ofa- tumumab in combination with CHOP for newly diag- nosed RT, where patients who received no prior CLL treatment had significantly better OS (median unreached at 24 months vs. approx. 6 months).32 A recent Danish National CLL Registry study of RT (over 8 years with mul- tiple histologies) also showed similar results, with a medi- an OS of 6.16 year in patients with untreated CLL versus 1.49 years in patients with treated CLL.11 The observed OS differences in these studies may be due to different biolo- gy in untreated patients. Further to this finding, RT patients who received only one line of CLL therapy had a trend of better OS compared to those who received two
or more lines of prior CLL therapies in our study, and two other studies also demonstrated that fewer lines of prior CLL therapy was associated with better RT survival,18,19 supporting the hypothesis that less therapy of CLL may be associated with less chemoresistance of RT. Of note, patients who were diagnosed with CLL and RT within three months (defined as concurrent RT) had a particularly favorable outcome, with a median OS of approximately six years. We suspect that the concurrent RT cases were more likely clonally unrelated (to the CLL) and resemble de novo DLBCL. This aspect warrants future studies. Based on our data, patients with concurrent RT may benefit from the typical therapy for de novo DLBCL.
TP53 disruption (i.e. del(17p) and/or TP53 mutation) was associated with a worse prognosis of RT in the uni- variate analysis, consistent with a number of prior studies.8,12,18,32-34 Of note, TP53 disruption was not an inde- pendent prognostic factor of OS in the multivariable analysis in our study. Rossi et al. showed that TP53 disrup-
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haematologica | 2020; 105(3)